Hydrogels are a class of materials formed from natural or synthetic polymers that exhibit three-dimensional (3D) networks with high to ultra-high degree of water content. While the term has been used as early as 1894, the first biological use of such gels was only reported by Wichterle and Lim in 1960. Since then, there has been an explosion of investigations documenting the use of hydrogels in many biomedical applications, including medicine and protein delivery, tissue engineering, cell culture, coatings and wound dressing. The methodologies involving the production of such materials have also seen substantial increase in recent years especially with regards to the type of physical and chemical cross-linking processes.
Hydrogels produced from the self-assembly of synthetic polymers have an inexhaustible potential to serve as delivery matrix for localized administration of theranostic components. Recent developments in polymer chemistry have enabled polymers to be synthesized with well-controlled composition and architecture. Highly versatile orthogonal functionalization strategies also allow gelation of such polymers and containment of payload through one or a combination of the following association mechanisms such as hydrophobic interactions, ionic interactions, hydrogen bonding, physical entanglement of macromolecules and chemical cross-linking of the matrix. A number of physical gel systems have been formulated using the ‘ABA’-type triblock copolymers and the polymeric amphiphiles can be designed with either the ‘A’ or ‘B’ constituent blocks to be hydrophilic or hydrophobic. Many of such systems engages the use of poly(ethylene glycol) (PEG) as the uncharged hydrophilic constituent block due to its biocompatibility. Some commonly used hydrophobic components include biodegradable poly(L-lactic acid) (PLLA), poly(L-glycolic acid), poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone). They can either form the middle ‘B’ block (e.g. PEG-PLGA-PEG) or as the terminus ‘A’ blocks (e.g. PLLA-PEG-PLLA). Aqueous mixture of enantiomeric triblock copolymers (e.g. PLLA-PEG-PLLA and PDLA-PEG-PDLA) could also form physical gels via stereocomplexation. Most ‘ABA’-type polymers require high concentration and/or hydrophobic content for hydrogel formation. For instance, PLLA-b-PEG-b-PLLA containing high lactide content of 17 to 37 wt. % require a minimum concentration of 16 wt. % for gelation. Such high hydrophobic compositions can give rise to adverse physiological effects during in vivo degradation. Thus, it is desirable to develop biodegradable polymeric materials that can form hydrogels at a low concentration.